title: Relationship between responsiveness to erythropoiesis-stimulating agent and long-term outcomes in chronic hemodialysis patients: a single-center cohort study.
abstract: BACKGROUND
  Responsiveness to erythropoietin-stimulating agent (ESA) may be associated with mortality risk in hemodialysis (HD) patients. The aim of the present study was to assess the relationship between responsiveness to ESA and long-term outcome in chronic HD patients.
  
  
  METHODS
  Patients on HD therapy for more than 6 months were enrolled in this cohort study. The first year was used to assess the longitudinal dialysis status of patients; the subsequent years were used to assess the time-dependent risk of all-cause mortality. Hazard ratios were estimated using a Cox proportional model for the association between ESA dose and hemoglobin (Hb) level and mortality, adjusting for potential confounders. The ESA resistance index (ERI) was determined as the weekly weight-adjusted dose of ESA divided by Hb concentration. Patients were divided into three groups by tertiles of ERI.
  
  
  RESULTS
  Of the 320 subjects enrolled, 105 died during the follow-up period of 70.4 ± 29.0 months. When subjects were stratified by epoetin dose and Hb level into four groups, those who had low Hb despite a high dose of epoetin were associated with the highest risk of mortality among the four groups (adjusted hazard ratio 1.86; 95 % confidence interval 1.25-2.75). These highest risk subjects had older age, lower body mass index, and lower serum levels of albumin, triglyceride, and transferring saturation. The impact of serum albumin and serum ferritin on mortality risk in an adjusted Cox proportional hazards model was in accordance with low Hb and higher ESA. There was no significant difference between the mortality risk and tertile of ERI.
  
  
  CONCLUSIONS
  High ESA dose and low Hb level were associated with an increased risk of all-cause mortality. However, the responsiveness to ESA estimated by ERI was not related to mortality risk. These findings suggest that the responsiveness to ESA should be evaluated by different methods in HD patients.
authors.affiliation: Department of Medicine, Medical Center East, Tokyo Women's Medical University, Arakawa-ku, Tokyo, Japan.
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Ogawa
authors.forename: Himiko
authors.initials: H
authors.lastname: Shimizu
authors.forename: Ai
authors.initials: A
authors.lastname: Kyono
authors.forename: Masayo
authors.initials: M
authors.lastname: Sato
authors.forename: Tetsuri
authors.initials: T
authors.lastname: Yamashita
authors.forename: Kuniaki
authors.initials: K
authors.lastname: Otsuka
authors.forename: Kosaku
authors.initials: K
authors.lastname: Nitta
mesh_terms: D000368:Aged; D000740:Anemia / Q000097:blood / Q000188:drug therapy* / Q000209:etiology; D015415:Biomarkers / Q000097:blood; D004305:Dose-Response Relationship, Drug; D004351:Drug Resistance; D004921:Erythropoietin / Q000008:administration & dosage* / Q000627:therapeutic use; D005260:Female; D005293:Ferritins / Q000097:blood; D006397:Hematinics / Q000008:administration & dosage* / Q000627:therapeutic use; D006454:Hemoglobins / Q000378:metabolism*; D006801:Humans; D053208:Kaplan-Meier Estimate; D007676:Kidney Failure, Chronic / Q000097:blood* / Q000401:mortality* / Q000628:therapy; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000627:therapeutic use; D006435:Renal Dialysis / Q000401:mortality; D012189:Retrospective Studies; D012709:Serum Albumin / Q000378:metabolism; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D015415:Biomarkers; D006397:Hematinics; D006454:Hemoglobins; D011994:Recombinant Proteins; D012709:Serum Albumin; C103998:epoetin beta; D004921:Erythropoietin; D005293:Ferritins